R-Lipoic HPLC Plasma Study

First time to be presented to the general public - as promised. Sure to generate a lot of interest for those people using an r-lipoic acid or considering it.

If you don't like or believe the results, invest in a HPLC study of your own and then post your results. This chart was one of many on display at GeroNova's exhibit at the American Aging Association meeting last weekend. There were a couple hundred PhD scientists viewing the research made available by GeroNova at their exhibit. Would you as a company subject yourself to that kind of peer scrutiny if you didn't have some credible research going on? Please keep that in mind before you challenge what I present.

Lot's of unstable R-lipoic on the market. Expect some spirited comments.

Plasma Study

More to come from Relentless Improvement over the next few weeks.

Pete

Pete,

1. Why does the hand filled cap have a lower peak--by an order or magnituede then the commercial peak?

2. The graph looks at plasma levels which implies the stuff is freely diffusable and not taken up in the cells and sequestered (the stuff does work in the mitochondria). Is this an appropriate model?

I know I'm in the minority, but I take AOR R-ala. I'm...skeptical.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

Oh and was the commercial R-ala from K=-mart or....?

I'm posting this here because whenever I edit a post twice....HTML hell.

The hand filled VS commercial filled looks highly suspicious to me.

Hi Scott,

Sorry for the delay. Great questions! As a skeptic myself, I appreciate your position. I will have answers for you, in an edited version of this post, as soon as possible. Please bear with me as I can't monitor the forum as often as I like, and I want to verify the accuracy of my response.

late edit-

stellar, for some reason I am under the impression that you have a business interest relating to supplements. Is that correct? If so, it is important to disclose so that your comments can be weighted appropriately. If not, sorry for the misunderstanding.

Thanks,
Pete

Edited by psychenaut, 10 June 2005 - 11:12 PM.

stellar, for some reason I am under the impression that you have a business interest relating to supplements. Is that correct? If so, it is important to disclose so that your comments can be weighted appropriately. If not, sorry for the misunderstanding. 

Thanks,
Pete

LOL pete!!

Thats a very interesting accusation that you throw out there, with no proof. I purchase my supplements from 1FAST400, CNW and BAC. I used to buy from Smi2le as well.

I merely stated my opinion that the comparison between "hand filled" and "commercial filled" looked suspicious. Instead of addressing the question, you accused me of having a "business interest". A good businessman would have addressed the question, rather than throw out a baseless accusation (a "sorry" doesn't negate it). Being a sponsor of this forum, don't you think you should be careful of turning off potential customers?


What happened to the image I hotlinked to on your blog?


EDIT: I reposted it, but due to Relentless Improvement's heavy handed techniques, I have removed the image.
Apparently he can't answer the question, so legal threats must be made. It's a rather simple question, a good retailer would answer it rather than throw out accusations and threats.

Edited by stellar, 11 June 2005 - 03:54 PM.

Pete,

AORsupport (I do not know his real name) posted many times on the board. Although some of my colleagues might disagree I do not think his presence was in any way heavy handed (speaking in terms of selling)...while he did mention his products from time to time it was with a rather soft sell. Obviously you support the forum and it is reasonable for you to be able to post and suggest your products. But as I started to write a post defending you from some of Zoolander's comments, I started thinking. Your style for better or worse is...a bit more heavy handed then AORsupport or that we are used to. You might bristle less feathers if you were a little softer in style.

Please do not misunderstand. Your choice of brands (LEF, AOR, Jarrow) suggest a commitment to providing quality products that people would benefit from.

So does this mean those who ingest K-R-ALA or Potassium-R-ALA should ingest it after a meal, 3 times daily? This might even out plasma levels over the course of a day I would imagine. I simply cannot afford GeroNova Research K-R-ALA, being a poor student, so I must cap my own from bulk sources such as 1fast400, etc.

Do you think I could mix creatine monohydrate powder with Potassium-R-ALA powder and place it in the same cap for a month without undue polymerization/reactions occurring? What other oft-supplemented nootropic ingredients might work well immediately touching Potassium-R-ALA for extended periods of time in the same cap?

Thank you,

-John

John you can get bulk geronova KALA from...forget if it is nutraplanet or custom nutrition warehouse.

Hi all,

Again, apologies for the late reply. I should have mentioned this is only one slide of a 70+ page presentation, more of which I can make available in a few weeks from now. There will be science aplenty, just hang on. I found this slide quite compelling, obtained permission to make it public, and wanted to share ASAP.

Scott,

1. Why does the hand filled cap have a lower peak--by an order or magnituede then the commercial peak?

The hand filled caps has a lower peak than the dex because it is not stabilized, and the peak for hand-filled is higher than the commercial caps as they have not been through the processing/capping machines, etc. and the dex is a salt form and is more readily absorbed.

2. The graph looks at plasma levels which implies the stuff is freely diffusable and not taken up in the cells and sequestered (the stuff does work in the mitochondria). Is this an appropriate model?

Measuring it in the cell is the next step, it has never been done before and, soon, it will be yet more new ground broken. Concentrations in the cell are usually 3-4 times higher than in the plasma, and the level in the plasma is an indication of how much there is in the cell, so there is plenty in the cell even though it is seen it in the plasma. Though the chart looks high, it is really only a tiny amount, mg/ml is very little.

Oh and was the commercial R-ala from K=-mart or....?

Chuckle...It was from a "leader in science backed dietary foods and supplements". That is all I can say at this point.

Scott, I sincerely appreciate your feedback and the comments on my posting style. Let me work on my approach on this forum, as I do a disservice to my message if I alienate my audience. I have a great zeal and enthusiasm for my work and the companies and products that I represent, and sometimes that comes across as heavy-handed. AORSupport is a person that I greatly admire and who is comitted to the life-extension movement. He is a science guy, and I am a sales and marketing guy. Coming in here representing AOR product, I knew there would some association and that his class act would be damn tough to follow! Keep up the feedback and I promise I will try my best.

stellar, thanks for the courtesy of your reply. I didn't make an accusation, I simply asked if you had a business interest in the supplement business, and you didn't answer it.

The hand filled VS commercial filled looks highly suspicious to me.

That is not a question, nor is it even an throw-away comment of specific enough nature that I would have a clue on how to respond to.

But stellar, you now have bigger problems. Who gave you permission to appropriate copyrighted material and 1. post it here 2. upload it to a different server? Because if you can't conjure up that permission, you just committed a felony and admitted to it publicly. I clearly stated: "This is copyrighted material. You MAY NOT distribute or post this graphic on any other site, however you may link to this blog post-" Either you delete that uploaded graphic and remove any other links to that graphic or you will experience, firsthand, copyright law litigation.

Scott and everyone else, thanks again for the patience and understanding, I am personally mixing wildly disparate disciplines (science, sales, marketing, business management, and blogging!) and am bound to make mistakes and piss people off along the way. The bottom line is that I am committed to relentless improvement and communicating breakthroughs as I come across them. My life would be a lot easier if I chose to stick with the status quo, but my passion won't allow that.

Cheers!
Pete

stellar, thanks for the courtesy of your reply. I didn't make an accusation, I simply asked if you had a business interest in the supplement business, and you didn't answer it.

That is not a question, nor is it even an throw-away comment of specific enough nature that I would have a clue on how to respond to.

But stellar, you now have bigger problems. Who gave you permission to appropriate copyrighted material and 1. post it here 2. upload it to a different server? Because if you can't conjure up that permission, you just committed a felony and admitted to it publicly. I clearly stated: "This is copyrighted material. You MAY NOT distribute or post this graphic on any other site, however you may link to this blog post-" Either you delete that uploaded graphic and remove any other links to that graphic or you will experience, firsthand, copyright law litigation.

Hi Pete,


Let me review what you said "Stellar, for some reason I am under the impression that you have a business interest relating to supplements".

You said "I didn't make an accusation, I simply asked if you had a business interest".

However, saying "I am under the impression that you have a business interest relating to supplements" IS an accusation. Let's not play word games, Pete. It doesn't make you look good, but your responses to me have painted you in a bad light.

You have made the above statement without any proof. I thought that by saying I buy supplements from all the major retailers (BAC, CNW, 1FAST400 [and in the past, Smi2le])....that would be enough to convince a non-paranoid individual that I do not have any business interest. Let me state for the record: I do not have a business interest in the supplement industry, I am an informed consumer.

The simple question is, and you have failed miserably in answering it: Why is there such a differential in the numbers of hand filled vs commercial filled capsules WRT the plasma levels of geronova's ALA? Could a commercial filled cap really make THAT much of a difference? To me it looks suspicious. Questioning the legitimacy of such a graph is a viable criticism and rather than explaining, you have accused me of having commercial interests in the supplement industry. This makes you look bad.

Apparently I didn't see the copywright thing on your weblog, my mistake. I have removed it from my previous post. It is unfortunate that instead of explaining the graph (ie the variances b/t commercial filled vs hand filled), you choose to distract from the issue and make legal threats. A good businessman would exhibit patience and try to answer questions from potential customers. You have not, and this makes you look even worse.

Hopefully you wont waste any more time trying to put me on the defensive with the tactics that you have previously employed. Please, just answer the questions....let me state them again:

-Why is there such a differential in the numbers of hand filled vs commercial filled capsules WRT the plasma levels of geronova's ALA?
-Could a commercial filled cap really make THAT much of a difference?

What's missing here is "ALA commercial cap" and "K-R-ALA commercial cap". In my readings so far on ALA topic I concluded that let's call it normal ALA is pretty stable, but R-ALA is not. Therefore commercial capped R-ALA goes thru different processes where it simpy goes bad. I belive generic K-R-ALA would show similar plasma levels as Geronovas. Also, I belive plain normal commercial ALA would do much better than commercial R-ALA.

With the lessons learned that
(A.) I need to provide more detail, and be more patient with challenging questions and science
AND
(B) Posters cannot simply take copyrighted material,
let's keep this thread positive and on topic. The info is far too important to get lost in the dust.

Let me try to clarify the question of "Hand filled" vs "Commercial". I did a poor job of explaining this initially, and the chart is not clear. The commercial would be an example of a typical non-salt form RLA, polymerized to a degree by the processing/capping. The hand filled would be illustrative of a non stabilized but non-polymerized RLA, the Dex would be illustrative of a salt-form RLA (such as K-RALA powder).

da sense you make a great point in your post. You are absolutely correct that ALA is stable. And that is by virtue of the fact it is a racemic mixture. Until recently the only way to stabilize RLA was as ALA (containing SLA), or, as a salt-form: K-RALA.

(late edit) Yes da sense, you could take the ALA, but you have to take that much more of it to get the effective RLA portion AND in so doing subject your body's chiral receptors to the unnatural S enantiomer. Some believe this has the possibility, in worst case, actually damage those receptors.

The problem with this is that the stability was obtained as a "deal with the devil" - addition of excipient content (K-RALA, a lipoate form) or content un-natural to the body's receptors (SLA). The result is either lowered bioavailabiltiy of the RLA or severe peaking.

Peakiness- you max plasma levels in about 20-30 minutes, and drop back to baseline in about 1.5 hours. Peaking doses of RLA are not optimal to gaining the best effects of RLA. Some believe the sharp peaks may even tip the cells into a pro-oxidative state.

Duration of effect- think of any other substance you take for therapeutic effect, you usually want a nice long, flat curve of plasma level right? For example- an antibiotic.

Absolute values are not the issue here, the challenge is manifold:
1. Keep it stable in processing/capping. (polymerization issue #1)
2. Keep it stable in stomach acid. (polymerization issue #2)
3. Get rid of excipient content (who needs or wants that?)
4. Extend duration of effect. (optimization of plasma levels).

As of today, the ONLY solution to all the parts of the challenge is the MCT stabilized and transported RLA. This is the RALA-Gel (just RLA and D-Biotin) or Mito-GOLD (which adds R-Dihydro and Delta-Tocotrienol for a "beefed up" antioxidant action) products. The MCT stabilizes it, get the RLA to the entero-hepatic portal (adds the bioavailability factor), and also provides for the optimized plasma levels.

So... the tee-shirt should read: "Got MCT?" )

This optimization is the real key and the true breakthrough, and indeed is the whole point of the chart. Shame on me for not understanding that I needed to detail this out.

There are 7 different pages of very detailed science HERE. Yes, it is not easy, but once you think it through it is quite clear and makes perfect sense. Also keep in mind, this is research that has not been done by any other company. ALL sellers of ALA or RLA buy it from some supplier. GeroNova is the only USA manufacturer of RLA. As a manufacturer, you would expect them to have knowledge that bottlers do not.

Go easy on me folks, I am trying something on this forum never done before- acting as a conduit to provide realtime breakthroughs from a manufacturer. They invested time and money (and blood) to do this study. This stuff is usually kept undercover until released through official channels. GeroNova didn't have to make this chart available to me, nor did I have to make it available to you. By all means, be skeptical, but also understand this is just a peek behind the curtain, much more to come in the next weeks and months. If you think this is just marketing hype, I need to know, as this is a boatload of time and effort for me that I can spend in other ways.

Cheers,
Pete

Edited by psychenaut, 13 June 2005 - 09:28 PM.

Pete, I thank you for your time and your effort to explain things here (and probably others too). I personally belive that geronovas ala is one of the best (if not the best), and if i had more allocated money for supplements i would go with your mito gold.
But till than, I'm improvising, by currently using normal ALA (plan to switch to K-R-ALA) with 2 caps of fish or CLA oil. Maybe adding some MCT would make it even better.

Da Sense AVOID CLA. Search prior posts. Or here from Udo Erasmus' site:

The Norwegian food-authorities are now warning the following groups about the dangers of CLA:


GROUP DANGER
Pregnant Mothers Affects birth weight and height
Breast Feeding Mothers Reduces fat in mother's milk
High Cholesterol ------
Overweight and Diabetes 2 Insulin Resistance

This information was published on 16th January, 2004 in a full-page article in Aftenposten, the biggest “serious” (non-tabloid) newspaper in Norway. Here is the article in Norwegian Langauge: www.aftenposten.no

Norwegian authorities are now developing language for mandatory label warnings on CLA-containing products. Sellers will have print warnings on labels outlining groups who are in danger from using CLA.

In the following link to the Norwegian health-authorities you will find background/scientific assessment and press releases about this decision (in Norwegian): http://www.mattilsyn...ldinger/cla.php

Quite welcome da sense. Again, you are right on track by taking your lipoic with a high quality fat, very smart. The only hitch might be is that you really need to take the lipoic on an empty stomach for max absorbtion. Empty tummy + fish oil usually = fish burps or nausea. Maybe use coconut oil instead? Caution- simply adding an "external" MCT while beneficial, will NOT offer the optimization effect of the RALA-Gel or Mito-GOLD.

For your situation, let me make a suggestion- consider the KRALA Liquid which is 100% RLA, I offer some compelling price breaks on the 2 oz bottle, you lose most of the excipients in the KRALA powder, and it is much more bioavailable than the powder. Might be a financially sensible compromise. Keep in mind too, the KRALA powder is only 40% RLA, be sure factor that into your equation.

Hope that makes sense.
Pete

Pete, thanks a lot for your informative reply. Quite a different tone from your initial responses to me, I appreciate that.
Our initial disagreements are looked upon by me as a "speed bump"....cheers to the future

scottl yes i'm aware of those from other forums. Tough I'm not a female, and my total cholesterol level is almost defficient (ratio is good), not overweight and so on. But still I found no real benefits from CLA, it's just that I have some left, and i'm taking 2 caps per day (that's why no benefits probably

Are you talking about conjugated linoleic acid? Go to sci.life-extension on google groups and you will find some studies suggesting that CLA increases insulin resistance.

Just checking liquid KRALA it says:
"R-Lipoic Acid is better absorbed and remains in the plasma longer when taken with fish oils, also available on our site."
Anyway liquid KRALA deal is not bad, i might try it on my next restocking.

Pete,

I appreciate the effort and providing the science (now I need...to lock myself in a room and go thorough it). It would not shock me if there were some people who were..difficult (hell 2 or 3 people even gave AORsupport a hard time for being a salesman which you know basically was not the case).

Bottom line is that no one has to buy the stuff from you (or anyone) so there is no reason to be rude.

Indeed, the subject material is tough enough without added sturm und drang. Better to work together for a common goal. We can always disagree and yet be respectful to each other.

Oh yeah, wait till I start the thread on nitrone spin traps and N-tert-butyl hydroxylamine. AND I am going to be offering a Brand New (MCT-based) lipoic formulation (groan from the crowd) in less than a week. Ha! It is only going to get better.

[sweat]

"New (MCT-based) lipoic formulation "

OK you seriously need to provide a a score card on the diffences.

Yo, Pete... as you know from my postings on your blog and periodic orders, I've begun seriously investing in my own health as I finally realize it makes soooo much more sense than other things I've spent my hard earned $ on... its amazing what a 4 year old daughter has done to change this 55 year olds' priorities... While AOR and to a lesser degree, LEF products form my core program (& fill much of my shelves) I do procure NOW, Source Naturals and other companies products when it "appears" to make sense. I recently bought a large supply of "stabilized" KRLA powder caps from Doctors Best as the price was too good to resist at the time ( iherb). However, from perusing this emotion-laden topic (wheeeuuu!) am I to understand that my 100mg "Stabilized R-Lipoic Acid" is actually 40mg. of potassium salt and only 60mg Rlipoic? It states it is "R-Lipoic acid 100 mg (as Potassium R-Lipoate K-RALA TM)) and also lists 150mcg biotin. I'd go on except 2 finger treo-typing sucks! cheers, all [thumb]

The Doctors Best is GeroNova K-RALA (salt-form) powder product. GeroNova formulates that as 250mg K-RALA to supply the 100mg R-Lipoic. You actually had the ratio backwards, K-RALA is only 40% R-lipoic and 60% excipient material.

[g:)] Scorecard and Cliff's Notes for Dr. Scott:

In order of how the science has evolved:

ALA: possible excipients, peaks, un-natural enantiomer that potentially can block RLA receptors. Racemic-ALA has poor solubility and absorption from the GI tract as only 30% reaches the plasma vs. an iv dose.

Unstabilized RLA: Polymerization in processing. Polymerization in stomach. Wildly varying bioavailability, if at all. Is that a tiger you have by the tail or a stuffed animal? No way to know.

K-RALA Powder (salt forms): State of the art two years ago. A stabilized RLA, but you are ingesting excipient content and getting the peakiness.

K-RALA-10 Liquid: State of the art for a lipoate liquid form RLA. Stable, Easily dissolved in water (K-RALA is Not), Greatly reduced solvent residues, Increased plasma levels (bioavailability is 12% higher than solid dosage forms). BUT- Peaky. Also good for those wishing to carefully titrate dosage (use in children, heavy metal chelation). Superb in water bottle before and during oxidising activities (stress/exercise). Take 300mg 5 minutes before a workout for an endogenous ATP blast. Comment- 15 or more minutes in water bottle can smell sufurous.

RALA-Gel: Current state of the art. Proprietary stabilization, MCT allows entero-hepatic transport for superb bioavailability and plasma level optimization. RALA-Gel is pure and EXCIPIENT FREE. Ingredients: 100mg RLA, MCT, 350mcg D-Biotin. Plasma levels optimized over at least 4-5 hours (may be as long as 6-7 hours). New study to be done to quantify exactly how long. Excellent for anti-aging and blood sugar control. Frequently used by diabetics.

Mito-GOLD: Current state of the art. Like RALA-Gel but is 75mg RLA and adds 75mg R-DHLA for "supercharged" antioxidant action and ATP activity. Also adds DeltaGOLD® D-Tocotrienol for cholesterol benefits, lowers triglycerides, and cardio benefits and synergistic antioxidant protection. D-Toco shows tumor-inhibition activity in several in vitro studies. D-Tocotrienol= very expensive substance. Frequently used by diabetics.

R-PLUS: Current state of the art. Brand new, I will have my initial inventory tomorrow. 75/75 RLA/R-DHLA like Mito-GOLD but no D-Tocotrienol for those either seeking to save $ or not needing added cardio benefits. Uses MCT transport for plasma optimization. Priced between Mito and Gel.

Now that you all unstand this by heart... let me introduce a new subject- the blood sugar control of a plasma optimized RLA. A lot of antiaging research is focusing on insulin and blood sugar in the aging process. More later, I have been doing this post intermittantly for 4 hours.

Pete

Thanks very much Pete.

BTW you mentioned...D biotin somewhere...have you seen this product?

http://www.designers.../flash_site.php
Glusophase (cute play on the drug name glucophage)
Supplement Facts
Serving Size: 1 Capsule
Servings per Container: 90
Amount Per Serving
K-R-Ala (Potassium-R-Lipoate)..........250mg
D-Biotin..........500mcg
Quercetin...........200mg
Q3D.....24mg
Q4D........25mg

Scott

Quite welcome Doc, and nice catch- that product at $59.99 makes my offerings look like bargain basement pricing. That product makes sense, but again, it is based on KRALA powder, not optimal. And, don't know if it is GeroNova product in the formula. (UPDATE EDIT, GeroNova does make this product for them) Their site does have the science right, kudos to them.

D-Biotin is in both Mito-GOLD and RALA-Gel:
"MITO-GOLD includes optically pure D-Biotin, as chronic administration of lipoic acid can lower the activities of pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase in vivo by competing with biotin."

The writeup on their site regarding effects on insulin and blood sugar appear, again, to be good science and I applaud them. They did their homework. RLA is noted in research as:
"an oral anti-hyperglycemic agent that improves peripheral glucose intake and utilization".

I am so far behind on a ton of stuff, and I may not be able to check the forum for a few days so always feel free to email me. That 70+ page fully referenced powerpoint will be available before month end. Do you think there is any interest in it?

Cheers,
Pete

Edited by psychenaut, 16 June 2005 - 01:03 AM.

Pete,

We'll still be here.

As far as the 70 pge writeup, I would be and I would imagine a few others also.

Thanks again for the info.

The hand filled caps has a lower peak than the dex because it is not stabilized, and the peak for hand-filled is higher than the commercial caps as they have not been through the processing/capping machines, etc. and the dex is a salt form and is more readily absorbed.

Actually, the hand filled caps contain R-ALA that is very fat soluble but has very little water solubility. The salt is water soluble, and thus can more readily be absorbed. The peak for hand-filled is indeed higher than the commercial caps, but this is because the commercial caps are more densely packed, and since R-ALA is fat-soluble with almost no water solubility, the more densely packed R-ALA is more likely to form a "clump" as it enters the small intestine if not administered with fatty food and oil. The R-ALA gel shows these results because the R-ALA is dissolved in a stable, high-quality fat medium.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

"R-ALA gel shows these results because the R-ALA is dissolved in a stable, high-quality fat medium."

So it is like the coenzyme Q-10 caps where the co Q-10 comes in an oil filled cap (like vit e)? Interesting.